Aldeyra Therapeutics, Inc.

Hello everyone and welcome to the LDRI Rhetorical TICS Phase 3 data call. My name is Carla and I will be coordinating your call today. During the presentation you will have the opportunity to ask questions by pressing star followed by 1 on your telephone keypad. If you change your mind, please press star followed by 2. I would now like to hand over to Laura Nichols to begin. Laura, please go ahead when you're ready.

Thank you and good morning everyone. Yesterday we issued a press release announcing achievement of the primary endpoint of a Phase 3 dry eye chamber trial of aproxilap, an investigational new drug for the treatment of dry eye disease. A copy of the press release is available on the investor in media section of our website .eldera.com. The press release contains important information and should be read and considered in conjunction with the slides presented in prepared remarks made on today's call. With me today to discuss the top line results is Dr. Todd Brady, President and Chief Executive Officer of ELDERA. Turning to slide 2. This presentation in various remarks, which may be made during this presentation, contain forward looking statements regarding ELDERA, its investigational drug candidate aproxilap, and its plans, expectations, and opportunities, including regulatory and commercial activities. Forward looking statements involve known and unknown risks, uncertainties, and other factors that may cause ELDERA's actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward looking statements. These statements are based upon the information available to ELDERA today and reflect ELDERA's current views with respect to the future events and are based on assumptions and subject to risks and uncertainties, including the outcome and timing of the FDA's review, acceptance, and or approval of a potential NDA resubmission for aproxilap and the adequacy of the data contained therein. ELDERA assumes no obligation to update oral or written statements made today as circumstances change. Future events and actual results could differ materially from those projected in the company's forward looking statements, including the results of operations and financial position. Additional information concerning factors that could cause results to differ materially from our forward looking statements are described in greater detail in the press release issued this morning. And in our filings with the Security and Exchange Commission. I would now like to turn your attention to slide three and introduce Dr.

Brayden. Thank you, Laura. We are thrilled to announce positive results from our second phase three dry eye chamber trial to assess the activity of aproxilap and reducing ocular discomfort associated with dry eye disease. Like the prior dry eye chamber trial relative to vehicle treatment, there was a highly statistically significant reduction in ocular discomfort following treatment with topical ocular aproxilap. And the results provide further support for a number of clinical trials, highlighting the potential rapid clinical effect of aproxilap on reducing ocular discomfort and we hope will enable NDA resubmission mid year. To our knowledge, aproxilap remains the first investigational drug with pivotal data supportive of acute and chronic activity in reducing symptoms of dry eye disease. As a way of background following review of a new drug application or NDA of topical ocular aproxilap for the treatment of dry eye disease, the FDA issued a complete response letter November of 2023, which stated that at least one additional adequate and well controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye needed to be conducted. The letter did not identify any other review issues. Following FDA feedback under the special protocol assessment program and based on additional comments, we initiated a phase three dry eye chamber trial designed to satisfy the FDA's resubmission requirements. The trial achieved the primary endpoint for proxilap statistically reduced ocular discomfort relative to vehicle. The NDA was resubmitted in October of last year. And last month, the FDA again issued a complete response letter, which stated that at least one additional adequate and well controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye needed to be conducted. In particular, the letter identified ocular discomfort baseline differences across treatment arms. Based in part on feedback received from the FDA after the CRL, we completed a second dry eye chamber trial designed to assess the effectiveness of aproxilap in reducing ocular discomfort. The results announced yesterday were highly statistically significant in favor of aproxilap over vehicle and importantly, no notable differences in ocular discomfort baselines were observed between treatment groups. We also completed a field trial of aproxilap, which while numerically in favor of aproxilap and consistent with prior field trials did not reach statistical significance. We believe that the recently completed dry eye chamber trial addresses the FDA feedback following review of the previously completed dry eye chamber trial resubmitted in the NDA last year. We have submitted the results of the dry eye chamber trial announced yesterday to the FDA and have requested a type A meeting to discuss NDA resubmission. Pending the type A meeting, we expect to resubmit the NDA mid year consistent with prior guidance. The results of the phase three randomized double masked vehicle control dry eye chamber trial are presented on slide four. In the trial, which was substantially similar to that of the previously completed dry chamber trial, patients receive randomized treatment before and during a dry eye chamber of 100 minutes in duration. The dry eye chamber, which is included in draft FDA guidance for drug development and dry disease is a rigorously controlled low humidity environment. Designed to exacerbate dry disease signs and symptoms, which typically peak around 40 to 50 minutes after chamber entry. Unlike field trials, which typically require months of clinical testing and many clinic visits. The dry chamber allows for the elimination of variability in humidity, temperature airborne particulate matter, such as pollen, smoke or pollution. And other factors known to influence dry eye disease. Most importantly, the chamber allows for the acute assessment of changes in signs and symptoms over a period measured in minutes. In this case, 100 minutes versus weeks or months in field trials. The primary endpoint was ocular discomfort score reported by the patients on a scale of zero or no discomfort to 100 the most severe discomfort. During the dry eye chamber from 80 to 100 minutes after chamber entry. The FDA considers oculars comfort a symptom of dry disease and based on our conversations with the FDA regarding the phase three dry chamber trials and analyses also considers discomfort dryness and other commonly assessed symptoms to be substantially similar. Like the previously completed dry chamber trial, given that there were no sign requirements in the complete response letter for the NBA resubmission and thus we believe that sign requirements have been met. Ocular discomfort was the sole primary endpoint and there were no secondary or exploratory endpoints. The primary endpoint analysis was excess was assessed using a mixed model for repeated measures across five time points again from 80 to 100 minutes after chamber entry. A period beginning 30 minutes after the second and final dose of a proxy lap or vehicle administered 50 minutes after chamber entry. 116 patients were enrolled 58 receive a proxy lap and 58 received vehicle. The primary endpoint of the phase three dry chamber trial was achieved with a P value of 0.002. Although symptoms do not immediately exacerbate after chamber entry and instead exacerbate over time. Oculars comfort score change from baseline was numerically lower with a proxy lap treatment than with vehicle treatment for all time points within the chamber and all time points during the primary assessment period from 80 to 100 minutes following chamber entry. The oculars comfort scores of patients treated with vehicle escalated consistently throughout the chamber. In contrast, oculars comfort scores of patients treated with a proxy lap. escalated at a lower rate after the first dose of drug indicating prophylactic activity of a proxy lap and it is substantially lower rate after the second dose of drug indicating treatment activity of a proxy lap. During the primary endpoint assessment period, the peak change from baseline in the proxy lap group was more than eight fold lower than that of the vehicle group. There were no safety concerns identified and reproxy lap was observed to be well tolerated no patients discontinued the clinical trial due to adverse events. And consistent with other clinical trials of a proxy lap, the most common adverse event was installation site irritation, which was exclusively mild and most commonly lasted less than one minute. To our knowledge, the results from this and the previously completed dry chamber trials represent the first positive phase three clinical trials and dry chamber with a symptom as a primary endpoint. And therefore, we believe the results are uniquely supportive the potential acute clinical effect of a proxy lap and reducing ocular discomfort and dry disease. In aggregate, the results are supportive of the rapid symptom logic effect of a proxy lap and preventing exacerbation of ocular discomfort in a setting designed to mimic the flares characteristic of dry disease. An issue highlighted in the prior dry eye chamber trial NDA review was an imbalance in ocular discomfort baseline scores across treatment arms, which prior to the treatment chamber was as much as seven points. As illustrated on slide five, no notable differences in baseline scores across treatment arms were observed before either the screening chamber or the treatment chamber. Using a Bayesian approach, which models the probability of effectiveness slide six summarizes the results of the recently completed field trial in conjunction with the two other field trials that we've conducted with same dosing regimen. While the recently completed field trial did not reach statistical significance, the results numerically favored or proxy lap and in aggregate, the effect profile of a proxy lap is statistically favored. Over that a vehicle, we expect to submit the field trial results to the planned NDA as supportive. Dry disease remains a pervasive and debilitating disease that is growing in prevalence and the clinical need remains for treatments that work quickly with sustained activity. Slide seven highlights the unique rapid activity of a proxy lap, which represents a novel mechanism of action that based on the clinical data generated to date potentially influences inflammation. Veso motor control, which could affect redness and the sensation of discomfort on the ocular surface and patients with dry eye disease. Consistent with the prior dry disease chamber trial yesterday's top line data suggests that in contrast currently available therapies that require weeks or months for activity. Reproxy lab has the potential to reduce ocular discomfort within minutes and a dry chamber. As such, reproxy lab continues to represent a potential paradigm shift in the way dry patients could be treated relative to standard of care. Slide eight summarizes the basis for NDA resubmission of a proxy lap for the treatment of dry disease. Specifically, at least one symptom trial was required by the FDA for resubmission and the FDA provided feedback on the prior dry chamber trial. As part of the most recent NDA review and also the dry chamber trial announced yesterday, which achieved the primary endpoint without the baseline imbalance observed in the prior trial. Thus, we expect to resubmit an NDA mid year consistent with prior guidance. The resubmission review period is expected to be six months. To our there is knowledge and patients with dry disease for proxies. Lap is the first investigational drug with pivotal data, supportive of acute and chronic activity and reducing symptoms. And the first investigational drug for chronic administration with pivotal data supportive of acute activity and reducing ocular redness. As previously disclosed, we expect that we're proxies. Lap, if approved, could be the first dry disease drug for chronic administration. With a label that highlights acute and chronic reduction in symptoms and acute reduction in ocular redness, a dry disease sign of particular importance to patients. Our clinical and regulatory milestones are summarized on slide nine. In addition to the expected resubmission of the NDA. We expect a variety of trial initiations and completions and a number of diseases characterized by inflammation and metabolic dysfunction, including those that affect the retina, skin and central nervous system. For the remainder of 2025 we expect initiations of a phase two clinical trial and atopic dermatitis and a phase two, three clinical trial and retinitis pigmentosa. And I and D submissions for dry dry age related macular degeneration metabolic inflammation and over 2025 and 2026 we believe our catalyst news flow to be robust. Our pipeline is summarized on slide 10. In addition to dry disease, we believe that for proxies, which is the subject of an option agreement with at the has completed clinical development for allergic conjunctivitis pending further discussions with the FDA. If approved for dry disease allergic conjunctivitis, which is one of the most common ocular diseases worldwide could represent a supplemental NDA submission. If approved for both diseases, where proxies would represent the first drug for chronic administration that could be used to treat dry disease and allergic conjunctivitis to persistently disturbing conditions that frequently occurred together in the same patients. Importantly, we are well capitalized to execute on our pipeline based on prior guidance current cash cash equivalents and marketable securities of over a hundred million dollars as of December 31st. Are expected to support operations into 2027 including clinical trial results in alcoholic hepatitis atopic dermatitis retinitis pigmentosa dry age related macular degeneration show. And we are also expected to support operations into 2027 including clinical trial results in metabolic inflammation. Consistent with prior guidance or cash runway guidance does not include partnership or product revenue associated with her proxy lab. Operator, I would now like to open the call for questions.

Thank you. We will begin now the question and answer session. If you'd like to ask a question, please press star followed by one on your telephone keypad. If you change your mind, please press star followed by T. When preparing to ask a question, please ensure your devices are muted locally and our first question comes from Katherine Novak with Jones.

Hi, morning Todd. Always a pleasure to be on here talking about dry eye disease phase three studies. I'm wondering if you can give us a sense of why you think the field trial did not hit that SIG. You know, was there unusually high vehicle efficacy changes in methodology or powering assumption versus prior field trials anything you can give would be helpful.

Happy to comment on the field trial. Good morning, Katherine.

First

of all, I'm thrilled that the chamber trial worked in the way that it did because should the drug get approved on our label, we will have one field trial that the FDA has already reviewed and considered acceptable and a chamber trial. And as I mentioned in my prepared comments, the chamber trial highlights acute activity, whereas field trials highlight durable activity over many weeks. I think had the field trial work and the chamber trial failed. The label would have had to field trials for symptoms, which would be, at least in my opinion, commercially less advantageous for the reasons that I just mentioned. The dry eye trials in general are variable. I think that like the psychiatric diseases, most companies run a number of phase three trials to get one or two to work over a long period of time. There is considerable variability in environment, as I mentioned in the prepared comments, pollen, particulate matter, temperature, humidity are all factors that can vary and are impossible to control in field trial settings. I think this is one of the reasons why the FDA recommends in their draft dry eye guidance that chamber trials be used. Those factors can be rigorously controlled in dry eye chamber trials, unlike field trials. I would argue in general, and I think most people in the dry eye field would argue that the variability in field trials is considerable in dry eye disease. This is why we ran three trials to satisfy the FDA's requirement from last year of another positive dry eye trial.

Got it. And then if you can just maybe talk about how you think FDA will view the totality of the data. Specifically, any language in the CRL pertaining to the signs of dry eye, you know, since tranquility one failed, but we had subsequent positive studies on redness, you know, help us understand that they have any issue with having one failed or two positive studies to maybe see how they'll view the field versus the chamber trial.

Well, the FDA by law requires two trials to make a claim on a label. And as I said, my prepared comments for redness, we believe we've satisfied the sign requirement. Redness is a unique sign in that commercially it's important. It's important to patients. It may be the only dry. I find, as I said over the years that is important to patients. We all care about how our eyes look. The good news is in the first NDA review, the FDA gave us credit for two redness trials, even though there were some redness data that weren't as supportive as the two trials for which they gave us credit. I think the same thing applies here. And symptoms again, the law is sponsors must have two positive trials to make a claim on a label. That is why the complete response that are letters that one additional trial or at least one additional trial. Now we have provided two additional positive dry eye chamber trials. I think it's very clear from the FDA perspective, at least regarding our discussions with the FDA that for symptoms, a field trial can satisfy in combination with a chamber trial. The challenge last time, as you know, Catherine was that we had a baseline imbalance in our prior dry eye chamber trial. We were absolutely thrilled to see that that baseline imbalance did not occur in the trial that we announced yesterday. The results are positive. They are consistent. And I think, at least in my opinion, it's very, very clear that reproxolap is highly active relative to vehicle and preventing ocular discomfort exacerbation in a chamber, which mimics, as I mentioned, the kinds of flares that are characteristic of the disease.

Got it. Thanks for clarifying Todd and thanks for taking my questions.

My pleasure Catherine. Take care.

And our next question comes from Tom Shredder with BTIG.

Good morning. Congratulations. This newest trial, is the overall treatment effect about the same as the prior trial? I think it's considerably bigger. Is that right? And how do you explain that? And then one sort of nagging question, there's always a comment somewhere in your presentation about irritation with the drops. We've been hearing a little bit about that. How bad is it? Do you think it's a commercial issue? And do you ever have a patient that won't take the second drop, which I suppose is the most relevant question? Thanks.

Right. Thanks, Tom. Good morning. Good. Good questions. In every respect, the trial we announced yesterday is superior to the prior dry eye chamber trial, not only with regard to the lack of a baseline imbalance, but also with regard to the effect size. You are correct. If you go back and look at those data that we announced, I guess, in August of last year. The drug did better, proxelap did better relative to a vehicle than it did in the prior trial. I think the explanation for that kind of improved activity has to do with the variability of dry disease that I highlighted in response to Catherine's question. We also use a different chamber. The two dry eye chamber trials were conducted at different clinical sites that may have had something to do with the difference in results. The first chamber was performed in Canada. The second chamber was performed or executed here in the United States. Irritation is common with everything that goes into your eye. Whether it be a particular like pollen. Or a solution like shower water. Your eye is designed to let you know that there's something in it. So that you can get that something out of it. Every drug has some form of. Irritation you'll see on every label for any topical ophthalmic medication that the number one side effect is irritation. As I mentioned in my comments. The irritation is exclusively mild. There is no moderate. There is no severe and the most common duration is less than a minute. They think over 80% of patients. Would describe it over less than a minute. I'd like to remind people that the primary endpoint. Of the prior chamber trial and the primary endpoint of the current chamber trial is discomfort. So, whatever irritation there is. Is is quickly reversed relative to vehicle. Which has no drug in it, as you know. So, I think all that in combination suggests that for dry to these patients who are used to taking eye drops. All of which have irritation. We shouldn't see much of an issue here with the proxy lab.

Okay, great. Thanks for the color.

Thanks Tom.

And our next question comes from Matthew Caulfield.

Hi, Todd. Good morning. I'm excited to see the advancements this morning. I wanted to ask about the top considerations for timing and potential execution from the option agreement. And then separately, as we think about the dry landscape. What criteria could select patients as the best fit for receiving a proxy lab versus trying any alternatives in terms of kind of what that selection process could look like. Thanks again.

Thanks, Matt. Good morning. Thanks for the kind words. I could talk about that last question for an hour, but I'll spare the audience. Let's talk about timing. First, I'll focus on NDA submission and then I'll touch on the disclosed option agreement with ADVI. The submission of the NDA is planned for mid year. That's consistent with our prior guidance. As I mentioned in my prepared comments, we've taken the somewhat unusual step of submitting the data from this trial announced yesterday to the FDA. I think that is an important and strong signal that the data from this trial are at least from our perspective valid and strong. And then we intend to discuss those data in a type A meeting that we have requested. As you know, after you receive a CRL, you have the opportunity within 90 days to request a type A meeting. Once that request goes in, the meeting is held within 30 days. The agenda of that meeting essentially is in the last NDA review of a dry eye chamber trial, you highlighted an issue that had to do with baseline imbalance primarily. And here are our data. Here are the results from another dry eye trial that are consistent with the prior dry eye chamber trial. We performed both trials at different locations. And as I said in response to Tom's question, as Tom highlighted, the differences between drug and vehicle are even more significant in this trial. So, in a sense, we do plan to submit mid year based on this type A meeting. And the idea is just to make sure with the FDA that the prior review really doesn't apply to the data from the trial we announced yesterday. ABB as we have publicly disclosed and this agreement is actually been filed, has the right to exercise an option to a co-development co-promotion agreement for ReproxalApp for all indications. That option expires 10 days after approval whenever approval occurs. If we submit mid year, we expect for the review to take six months, which is per protocol for the FDA for NDA resubmissions. And so should the drug be approved, then ABB would have 10 days to exercise the option. Finally, the idea that there are other dry eye products out there available for patient use relative to our new potential new entrance of ReproxalApp is interesting. I think, as I said in my prepared comments, there are really no good options that have been proven to work quickly. No one wants to wait two weeks for activity. No one wants to wait four weeks for activity. And so there's a real opportunity in the dry eye market for a drug that works quickly. And that is what the data suggests from the trial announced yesterday and the prior dry eye trial that at least there is the potential for a ProxalApp to make patients feel or potentially look better within minutes. That is a paradigm shift. That is what we tried to highlight on slide seven. Not withstanding what we hope is a temporary delay in approval for a ProxalApp where ProxalApp remains the only drug in our perspective that has proven acute activity. Which patients would qualify? Well, I guess those patients that want acute activity, which is more or less all patients. I don't see any reason why physicians or optometrists would segment patients for one particular drug over another. Patients are customers and most patients want to feel better now, not later.

Excellent. Very helpful. I really appreciate that.

Yeah, thanks, Matt.

Just as a reminder, if you'd like to ask a question, is star one on your telephone keypad. Our next question comes from Neil Jen with Laylo and Company.

Good morning, Todd and congrats on the outcome. Just two questions here. The first one is for the field trial that shows week one to six. I'm just curious whether that's average, the measurement over average of each week or just to the end of the data study period.

Right, Yale, the data on

slide six for the field trials really is designed to show the aggregate effect of three field trials. The one we announced yesterday in addition to two prior 12 week trials. As you correctly point out, the one announced yesterday was six weeks in duration. The prior field trials were 12 weeks in duration. Which is why the x axis on that graph says weeks one through six. Just look at the first six weeks where the bulk of activity seems to occur. I think you get a very robust effect profile when considering all trials in aggregate.

Okay, great. That's very helpful in the details. And then maybe one more question here, which is that it's sort of clear that the proctor lab has a very acute effect. And also you mentioned about the chronic effect value. So would you elaborate a little bit more on that? Given the most of the drug, it's only on the chronic one, but not necessarily acute treatment effects.

Correct. Yes, not withstanding my highlighting the acute activity of a proctor lab, the drug will be approved for chronic administration. And dry disease that I'm aware of the only drug that's not approved for chronic administration is an ocular steroid, a topical steroid, which you can't use chronically due to toxicity concerns, which include cataracts and and glaucoma among other issues. The chronic activity or the durability of the proctor lab really is highlighted in the field trials and to your previous question, the data on slide six or sort of the average reflect the average over six weeks of use. And the field trial that is reviewed and found acceptable already is a twelve week trial. So I think we have relative to our competition, but plenty of chronic data that support durability. And now I would say to symptom trials in a dry chamber that support acute activity.

Okay, great. This is a very helpful and again, congrats on the data. And the best for the next patient.

Thank you. Yeah.

And our next question comes from Kelly to you with Jeffrey.

Good morning, Todd. This is Jose for Kelly. Thanks for taking my question. It's more of a clarification question. When FDA raised concerns about baseline differences. Between the placebo and treatment arms, were they referring to the first measurement post chamber entry, either screening or treatment specifically, or was it differences in baseline prior to end chamber entry? And also on the type a meeting, I believe you mentioned you had already been scheduled for 30 days last month. Is it very dissimilar happening soon or is it to get pushed back? Any colleague can provide a natural will be helpful.

For sure.

Thanks.

Let me begin with the type a meeting. I'm glad you brought that up. After the CRL last month, the FDA provided further feedback on the two trials. That we announced yesterday and because the FDA provided for the feedback, which was productive and allowed us to lock the databases and read out the trials. We no longer needed to hold a type a meeting immediately after the CRL. So we switched strategy to go ahead, read out the trials based on the feedback provided from the FDA and then discuss the data from the trials. At the type a meeting, as I mentioned in my prepared comments, that meeting has been requested

and

the data from the chamber trial announced yesterday has been submitted directly to the FDA. Your first question was about baseline differences. As you pointed out, there are two chambers in these trials. There is a screening chamber where patients receive vehicle. And there is a randomized treatment chamber where patients are first randomized and then either receive vehicle or reproxal app. Thus, there are two baselines. There is a baseline before the screening chamber and there is a baseline before the randomized treatment chamber. An illustration of that is on slide five. Where the two baselines are plotted across treatment arms for the trial that was announced yesterday. In the previous dry eye chamber trial, the FDA noted a seven point difference before the randomized treatment chamber. Which is not ideal. Typically, sponsors account for baseline differences by controlling for baseline in a statistical model as a covariate. You also attempt to mitigate differences in randomization and baseline by randomizing a subject, but sometimes, particularly in smaller trials of 100 subjects or so. You will see by chance differences in baseline. I believe the FDA's point in the last NDA review was because of this baseline difference, it's difficult to distinguish the effective drug from the effective baseline. Which is why we're thrilled to see the data on slide five. Where we have confirmed the previous dry eye chamber trial in terms of effect and statistical significance. Without any notable differences in baseline across treatment arms before either of the trials of the AI chambers.

Very helpful. Thank you.

Thank

you.

And that was our final question. So I will hand back over to Todd Brady for any final comments.

Well, thank you all for joining us this morning. We appreciate your time and interest in Aldera and as always, we look forward to updating you on further developments.

This concludes today's Aldera conference call. Thank you everyone for joining. You might now disconnect.